Sulforaphane improves endothelial function and reduces placental oxidative stress in vitro

Annie G. Cox, Seshini Gurusinghe, Rahana Abd Rahman, Bryan Leaw, Siow T. Chan, Joanne C. Mockler, Padma Murthi, Sarah A. Marshall, Rebecca Lim, Euan M. Wallace

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Introduction: The maternal endothelial dysfunction characteristic of preeclampsia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro. Methods: We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule; VCAM1, intracellular adhesion molecule; ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane. We also assessed the effects of sulforaphane in mitigating hypoxic and hyperoxic injury in term placental explants by measuring secretion of anti-angiogenic factors. To assess the role of NRF2 we silenced NRF2 in HUVECs and primary trophoblast cells. Results: Sulforaphane reduced TNF-α mediated HUVEC secretion of endothelin-1, VCAM1, ICAM1 and E-selectin, and prevented increased endothelial permeability. In placental explants, sulforaphane reduced the secretion of soluble Flt-1, soluble endoglin and activin A. Sulforaphane induced activation and nuclear translocation of NRF2 in HUVECs, inducing heme oxygenase 1. NRF2 silencing blocked some but not all of sulforaphane's effects in HUVECs. NRF2 silencing did not prevent sulforaphane's inhibition of trophobast secretion of soluble Flt-1 or activin A. Conclusion: In reducing placental and endothelial oxidative stress, sulforaphane may offer a new adjuvant therapeutic approach for the treatment of preeclampsia.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalPregnancy Hypertension
Volume16
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • Endothelial cell
  • NRF2
  • Oxidative stress
  • Preeclampsia
  • Sulforaphane
  • Trophoblast

Cite this

Cox, Annie G. ; Gurusinghe, Seshini ; Abd Rahman, Rahana ; Leaw, Bryan ; Chan, Siow T. ; Mockler, Joanne C. ; Murthi, Padma ; Marshall, Sarah A. ; Lim, Rebecca ; Wallace, Euan M. / Sulforaphane improves endothelial function and reduces placental oxidative stress in vitro. In: Pregnancy Hypertension. 2019 ; Vol. 16. pp. 1-10.
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abstract = "Introduction: The maternal endothelial dysfunction characteristic of preeclampsia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro. Methods: We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule; VCAM1, intracellular adhesion molecule; ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane. We also assessed the effects of sulforaphane in mitigating hypoxic and hyperoxic injury in term placental explants by measuring secretion of anti-angiogenic factors. To assess the role of NRF2 we silenced NRF2 in HUVECs and primary trophoblast cells. Results: Sulforaphane reduced TNF-α mediated HUVEC secretion of endothelin-1, VCAM1, ICAM1 and E-selectin, and prevented increased endothelial permeability. In placental explants, sulforaphane reduced the secretion of soluble Flt-1, soluble endoglin and activin A. Sulforaphane induced activation and nuclear translocation of NRF2 in HUVECs, inducing heme oxygenase 1. NRF2 silencing blocked some but not all of sulforaphane's effects in HUVECs. NRF2 silencing did not prevent sulforaphane's inhibition of trophobast secretion of soluble Flt-1 or activin A. Conclusion: In reducing placental and endothelial oxidative stress, sulforaphane may offer a new adjuvant therapeutic approach for the treatment of preeclampsia.",
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author = "Cox, {Annie G.} and Seshini Gurusinghe and {Abd Rahman}, Rahana and Bryan Leaw and Chan, {Siow T.} and Mockler, {Joanne C.} and Padma Murthi and Marshall, {Sarah A.} and Rebecca Lim and Wallace, {Euan M.}",
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Sulforaphane improves endothelial function and reduces placental oxidative stress in vitro. / Cox, Annie G.; Gurusinghe, Seshini; Abd Rahman, Rahana; Leaw, Bryan; Chan, Siow T.; Mockler, Joanne C.; Murthi, Padma; Marshall, Sarah A.; Lim, Rebecca; Wallace, Euan M.

In: Pregnancy Hypertension, Vol. 16, 01.04.2019, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Gurusinghe, Seshini

AU - Abd Rahman, Rahana

AU - Leaw, Bryan

AU - Chan, Siow T.

AU - Mockler, Joanne C.

AU - Murthi, Padma

AU - Marshall, Sarah A.

AU - Lim, Rebecca

AU - Wallace, Euan M.

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N2 - Introduction: The maternal endothelial dysfunction characteristic of preeclampsia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro. Methods: We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule; VCAM1, intracellular adhesion molecule; ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane. We also assessed the effects of sulforaphane in mitigating hypoxic and hyperoxic injury in term placental explants by measuring secretion of anti-angiogenic factors. To assess the role of NRF2 we silenced NRF2 in HUVECs and primary trophoblast cells. Results: Sulforaphane reduced TNF-α mediated HUVEC secretion of endothelin-1, VCAM1, ICAM1 and E-selectin, and prevented increased endothelial permeability. In placental explants, sulforaphane reduced the secretion of soluble Flt-1, soluble endoglin and activin A. Sulforaphane induced activation and nuclear translocation of NRF2 in HUVECs, inducing heme oxygenase 1. NRF2 silencing blocked some but not all of sulforaphane's effects in HUVECs. NRF2 silencing did not prevent sulforaphane's inhibition of trophobast secretion of soluble Flt-1 or activin A. Conclusion: In reducing placental and endothelial oxidative stress, sulforaphane may offer a new adjuvant therapeutic approach for the treatment of preeclampsia.

AB - Introduction: The maternal endothelial dysfunction characteristic of preeclampsia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro. Methods: We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule; VCAM1, intracellular adhesion molecule; ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane. We also assessed the effects of sulforaphane in mitigating hypoxic and hyperoxic injury in term placental explants by measuring secretion of anti-angiogenic factors. To assess the role of NRF2 we silenced NRF2 in HUVECs and primary trophoblast cells. Results: Sulforaphane reduced TNF-α mediated HUVEC secretion of endothelin-1, VCAM1, ICAM1 and E-selectin, and prevented increased endothelial permeability. In placental explants, sulforaphane reduced the secretion of soluble Flt-1, soluble endoglin and activin A. Sulforaphane induced activation and nuclear translocation of NRF2 in HUVECs, inducing heme oxygenase 1. NRF2 silencing blocked some but not all of sulforaphane's effects in HUVECs. NRF2 silencing did not prevent sulforaphane's inhibition of trophobast secretion of soluble Flt-1 or activin A. Conclusion: In reducing placental and endothelial oxidative stress, sulforaphane may offer a new adjuvant therapeutic approach for the treatment of preeclampsia.

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